Extracellular matrix molecules and cell adhesion molecules induce neurites through different mechanisms.
It has recently become clear that both extracellular matrix (ECM) glycoproteins and various cell adhesion molecules (CAMs) can promote neurite outgrowth from primary neurons, though little is known of the intracellular mechanisms through which these signals are transduced. We have previously obtained evidence that protein kinase C function is an important part of the neuronal response to laminin (Bixby, J.L. 1989. Neuron. 3:287-297). Because such CAMs as L1 (Lagenauer, C., and V. Lemmon. 1987. Proc. Natl. Acad. Sci. USA. 84:7753-7757) and N-cadherin (Bixby, J.L. and R. Zhang. 1990. J. Cell Biol. 110:1253-1260) can be purified and used as substrates to promote neurite growth, we have now tested whether the response to CAMs is similarly dependent on protein kinase C. We find that inhibition of protein kinase C inhibits growth on fibronectin or collagen as well as on laminin. In contrast, C kinase inhibition actually potentiates the initial growth response to L1 or N-cadherin. The later "phase" of outgrowth on both of these CAMs is inhibited, however. Additionally, phorbol esters, which have no effect on neurite growth when optimal laminin concentrations are used, potentiate growth even on optimal concentrations of L1 or N-cadherin. The results indicate that different intracellular mechanisms operate during initial process outgrowth on ECM substrates as compared to CAM substrates, and suggest that protein kinase C function is required for continued neurite growth on each of these glycoproteins.
Bixby
J L
JL
Department of Pharmacology, University of Miami School of Medicine, Florida 33136.
Jhabvala
P
P
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015820:Cadherins / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000302:isolation & purification / Q000494:pharmacology*; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D005726:Ganglia, Parasympathetic / Q000166:cytology; D007546:Isoquinolines / Q000494:pharmacology; D007797:Laminin / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015820:Cadherins; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D007546:Isoquinolines; D007797:Laminin; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate